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Editors Selection IGR 22-2

Neuroprotection: MK801

Makoto Araie

Comment by Makoto Araie on:

13521 Assessment of neuroprotective effects of glutamate modulation on glaucoma-related retinal ganglion cell apoptosis in vivo, Guo L; Salt TE; Maass A et al., Investigative Ophthalmology and Visual Science, 2006; 47: 626-633


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Compared to MK801 accepted as an anti-apoptotic agent against glutamate, neuroprotective effect of metabotropic glutamate receptor antagonist is still controversial. Guo et al. (203) investigated the neuroprotective effects of glutamate modulation with MK801, nonselective NMDA receptor antagonist, and LY354740, Class II metabotropic glutamate receptor antagonist using in vivo rat staurosporine induced apoptosis model. Combined treatment of MK801 and LY354740 was most effective to protect retinal ganglion cell apoptosis in staurosporine model, and also effective against ocular hypertension rat model. This combined glutamate modulation treatment is more effective and may be a safer neuroprotective therapy than MK801 single treatment. Further investigation should be needed to clarify the neuroprotective mechanism of metabotropic glutamate receptor subclasses including class II. in vivo apoptosis imaging with annexin-V to evaluate apoptotic cell death is a useful technique compared to immunohistological assessment, because real time in vivo imaging clues us in on appropriate time to evaluate apoptosis. However, in vivo apoptotic cells stained by intravitreally injected annexin-V must be finally counted by retinal flat mount images. Further efficient assessment with less invasive and simple procedures will be desirable.



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